O presente estudo foi realizado para investigar a relação entre forças hemodinâmicas locais e remodelamento intimal e medial nos segmentos pré-estenose e pós-estenose da parede da aorta abdominal de ratos submetidos à estenose acentuada. Foram utilizados ratos Wistar machos divididos em dois grupos: sham-operado, grupo controle em que a aorta foi apenas manipulada, e grupo estenosado, animais submetidos à cirurgia de estenose da aorta abdominal. As aortas demonstraram duas respostas remodeladoras distintas e diferentes ao estímulo hemodinâmico induzido pela coarctação infra-diafragmática. A primeira é o remodelamento no segmento pré-estenótico hipertensivo com tensão circunferencial da parede aumentada associada com estresse tensional normal, fluxo laminar e tensão de cisalhamento normal. As células endoteliais eram heterogêneas, aumentadas em tamanho e alongadas em direção ao fluxo. Além disso, observou-se conspícuas placas neointimais difusamente distribuídas e espessamento medial. Nossos achados sugerem que a tensão circunferencial da parede aumentada devido a hipertensão tem papel fundamental no remodelamento desse segmento através de efeitos biomecânicos sobre o estresse oxidativo e expressão aumentada de TGF-?. A segunda é o remodelamento no segmento pós-estenótico normotenso com fluxo turbilhonar e baixa tensão de cisalhamento na parede associados a tensão circunferencial da parede e estresse tensional normais. As células endoteliais apresentavam-se semelhantes aos controles, exceto por alterações fenotípicas focais associadas à presença de conspícuas placas neointimais focalmente distribuídas, similares mas muito maiores que as encontradas no segmento pré-estenose. Mais estudos são necessários para se determinar como as forças mecânicas do fluxo turbilhonar e da baixa tensão de cisalhamento na parede são detectadas e traduzidas em sinais bioquímicos para as células e convertidas em alterações fenotípicas patofisiologicamente relevantes. / The present investigation was carried out to evaluate the relationship between local hemodynamic forces and intimal and medial remodeling in the proximal and distal segments of the arterial walls of rats in relation to severe stenosis of the aorta. Male Wistar young rats were divided randomly into: operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Constricted aortas showed two distinct adaptive remodeling responses to hemodynamic stimuli induced by coarctation. The first is remodeling in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress. The remodeling in this segment is characterized by enlarged heterogeneous endothelial cells, elongated in the direction of the blood flow, diffusely distributed neointimal plaques, appearing as discrete bulging toward the vascular lumen, and medial thickening. Our findings suggest that increased circumferential wall tension due to hypertension play a pivotal role in the remodeling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-? expression. The second is remodeling in the normotensive poststenotic segment with turbulent flow/low wall shear stress and normal circumferential wall tension and tensile stress. The remodeling in this segment is characterized by groups of endothelial cells with phenotypic alterations and focally distributed neointimal plaques, similar but many of them larger than those found in the prestenotic segments. Further studies are needed to determine how the mechanical forces of turbulent flow/low shear stress are detected and transduced into biochemical signaling by the cells of the artery walls and then converted into pathophysiologic relevant phenotypic changes.

Ischaemic heart disease remains the single leading cause of death throughout the world. Rupture of an advanced atheromatous coronary plaque precipitates the majority of these clinical events, resulting in thrombosis and myocardial infarction. Post-mortem studies have identified thin-cap fibroatheroma (TCFA) as the plaque subtype most prone to rupture with prospective virtual-histology intravascular ultrasound (VH-IVUS) studies linking VH-TCFA to future adverse clinical events. VH-TCFA are however common along the coronary tree with the majority remaining clinically silent, suggesting that factors other than plaque phenotype play an important role in determining rupture and future plaque behaviour. Rupture is thought to occur when the structural stress within the plaque exceeds the material strength of the overlying fibrous cap. Previous histological work has demonstrated that ruptured plaques are associated with higher stress compared to non-ruptured controls, with in vivo VH-IVUS studies linking higher plaque structural stress (PSS) with the presentation of acute coronary syndrome. Wall shear stress (WSS) on the other hand has been implicated in early plaque development and plaque growth suggesting that both PSS and WSS can influence future plaque behaviour. The work presented in this thesis is associated with a number of novel findings. First, it is the only work to demonstrate that in vivo PSS is higher in coronary atherosclerotic plaques with rupture vs. no rupture across a range of plaque subtypes and irrespective of whether analysis of the entire plaque or of regions close to the minimal luminal area is performed. Second, it shows that the pattern and extent of plaque progression and regression defined as an increase and decrease in plaque area, respectively, are associated with specific biomechanical environments at baseline, in the only study that examines the role of both PSS and WSS in this process. More specifically, high PSS is associated with changes consistent with increased vulnerability both in areas of progression and regression. On the other hand, lower WSS at baseline is associated with greater increases in plaque area and burden in areas that progress and with smaller decreases in areas that regress largely due to changes in fibrous tissue. Although the role of WSS in determining future plaque behaviour has been previously examined, this is the first time that this is assessed specifically in areas of progression and regression, particularly important in view of the dynamic nature of atherosclerotic plaques. More importantly, the work presented in this thesis demonstrates that the interplay of these biomechanical forces is associated with specific patterns of plaque progression and regression despite the fact that PSS and WSS are independent of each other. This has never been previously demonstrated and further suggests that incorporation of biomechanical analysis can play role in the identification of plaques that lead to future clinical events. Finally, the ability of PSS to identify plaques that lead to adverse clinical events was assessed through a propensity core matched analysis of the PROSPECT (A Prospective Natural-History Study of Coronary Atherosclerosis) study. The analysis presented here is the largest, most extensive and thus most significant work to ever examine this with results suggesting that incorporation of PSS and associated parameters can improve the capability of VH-IVUS to identify plaques that lead to such events. In summary, the results of this thesis suggest that coronary PSS plays an important role in the pathophysiology of plaque rupture, and that its incorporation in routine plaque assessment may improve our current ability to identifying coronary plaques that lead to future adverse clinical events. The interplay between PSS and WSS may also affect future plaque behaviour and in particular progression and regression. Prospective studies are now required to fully evaluate the role of these biomechanical forces in plaque development, and whether their incorporation in plaque evaluation can be of clinical significance.

O presente estudo foi realizado para investigar a relação entre forças hemodinâmicas locais e remodelamento intimal e medial nos segmentos pré-estenose e pós-estenose da parede da aorta abdominal de ratos submetidos à estenose acentuada. Foram utilizados ratos Wistar machos divididos em dois grupos: sham-operado, grupo controle em que a aorta foi apenas manipulada, e grupo estenosado, animais submetidos à cirurgia de estenose da aorta abdominal. As aortas demonstraram duas respostas remodeladoras distintas e diferentes ao estímulo hemodinâmico induzido pela coarctação infra-diafragmática. A primeira é o remodelamento no segmento pré-estenótico hipertensivo com tensão circunferencial da parede aumentada associada com estresse tensional normal, fluxo laminar e tensão de cisalhamento normal. As células endoteliais eram heterogêneas, aumentadas em tamanho e alongadas em direção ao fluxo. Além disso, observou-se conspícuas placas neointimais difusamente distribuídas e espessamento medial. Nossos achados sugerem que a tensão circunferencial da parede aumentada devido a hipertensão tem papel fundamental no remodelamento desse segmento através de efeitos biomecânicos sobre o estresse oxidativo e expressão aumentada de TGF-?. A segunda é o remodelamento no segmento pós-estenótico normotenso com fluxo turbilhonar e baixa tensão de cisalhamento na parede associados a tensão circunferencial da parede e estresse tensional normais. As células endoteliais apresentavam-se semelhantes aos controles, exceto por alterações fenotípicas focais associadas à presença de conspícuas placas neointimais focalmente distribuídas, similares mas muito maiores que as encontradas no segmento pré-estenose. Mais estudos são necessários para se determinar como as forças mecânicas do fluxo turbilhonar e da baixa tensão de cisalhamento na parede são detectadas e traduzidas em sinais bioquímicos para as células e convertidas em alterações fenotípicas patofisiologicamente relevantes. / The present investigation was carried out to evaluate the relationship between local hemodynamic forces and intimal and medial remodeling in the proximal and distal segments of the arterial walls of rats in relation to severe stenosis of the aorta. Male Wistar young rats were divided randomly into: operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Constricted aortas showed two distinct adaptive remodeling responses to hemodynamic stimuli induced by coarctation. The first is remodeling in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress. The remodeling in this segment is characterized by enlarged heterogeneous endothelial cells, elongated in the direction of the blood flow, diffusely distributed neointimal plaques, appearing as discrete bulging toward the vascular lumen, and medial thickening. Our findings suggest that increased circumferential wall tension due to hypertension play a pivotal role in the remodeling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-? expression. The second is remodeling in the normotensive poststenotic segment with turbulent flow/low wall shear stress and normal circumferential wall tension and tensile stress. The remodeling in this segment is characterized by groups of endothelial cells with phenotypic alterations and focally distributed neointimal plaques, similar but many of them larger than those found in the prestenotic segments. Further studies are needed to determine how the mechanical forces of turbulent flow/low shear stress are detected and transduced into biochemical signaling by the cells of the artery walls and then converted into pathophysiologic relevant phenotypic changes.

<p>By applying a segmentation procedure to two different sets of computed tomography scans, two geometrical models of the abdominal aorta, containing one inlet and two outlets have been constructed. One of these depicts a healthy blood vessel while the other displays one afflicted with a Abdominal Aortic Aneurysm. </p><p>After inputting these geometries into the computational dynamics software FLUENT, six simulations of laminar, stationary flow of a fluid that was assumed to be Newtonian were performed. The mass flow rate across the model outlet boundaries was varied for the different simulations to produce a basis for a parameter analysis study. </p><p>The segmentation data was also used as input data to a surface description procedure which produced not only the surface itself, but also the first and second directional derivatives in every one of its defining spatial data points. These sets of derivatives were followingly applied in an additional procedure that calculated values of Gaussian curvature. </p><p>A parameter variance analysis was carried out to evaluate the performance of the surface generation procedure. An array of resultant surfaces and surface directional derivatives were obtained. Values of Gaussian curvature were calculated in the defining spatial data points of a few selected surfaces. </p><p>The curvature values of a selected data set were visualized through a contour plot as well as through a surface map. Comparisons between the curvature surface map and one wall shear stress surface map were made.</p>

By applying a segmentation procedure to two different sets of computed tomography scans, two geometrical models of the abdominal aorta, containing one inlet and two outlets have been constructed. One of these depicts a healthy blood vessel while the other displays one afflicted with a Abdominal Aortic Aneurysm. After inputting these geometries into the computational dynamics software FLUENT, six simulations of laminar, stationary flow of a fluid that was assumed to be Newtonian were performed. The mass flow rate across the model outlet boundaries was varied for the different simulations to produce a basis for a parameter analysis study. The segmentation data was also used as input data to a surface description procedure which produced not only the surface itself, but also the first and second directional derivatives in every one of its defining spatial data points. These sets of derivatives were followingly applied in an additional procedure that calculated values of Gaussian curvature. A parameter variance analysis was carried out to evaluate the performance of the surface generation procedure. An array of resultant surfaces and surface directional derivatives were obtained. Values of Gaussian curvature were calculated in the defining spatial data points of a few selected surfaces. The curvature values of a selected data set were visualized through a contour plot as well as through a surface map. Comparisons between the curvature surface map and one wall shear stress surface map were made.

An analytical study was performed to evaluate the effect of shear wall ratio on the dynamic behavior of mid-rise reinforced concrete structures. The primary aim of this study is to examine the influence of shear wall area to floor area ratio on the dynamic performance of a building. Besides, the effect of shear wall configuration and area of existing columns on the seismic performance of the buildings were also investigated. For this purpose, twenty four mid-rise building models that have five and eight stories and shear wall ratios ranging between 0.51 and 2.17 percent in both directions were generated. These building models were examined by carrying out nonlinear time-history analyses using PERFORM 3D. The analytical model used in this study was verified by comparing the analytical results with the experimental results of a full-scale seven-story reinforced concrete shear wall building that was tested for U.S.-Japan Cooperative Research Program in 1981. In the analyses, seven different ground motion time histories were used and obtained data was averaged and utilized in the evaluation of the seismic performance. Main parameters affecting the overall performance were taken as roof and interstory drifts, their distribution throughout the structure and the base shear characteristics. The analytical results indicated that at least 1.0 percent shear wall ratio should be provided in the design of mid-rise buildings, in order to control observed drift. In addition / when the shear wall ratio increased beyond 1.5 percent, it was observed that the improvement of the seismic performance is not as significant.

Το θέμα της παρούσης εργασίας είναι η μελέτη της μη μόνιμης αιματικής ροής στις στεφανιαίες αρτηρίες της καρδιάς σε φυσιολογική κατάσταση, με στένωση καθώς και με αποκατάσταση της ροής με αναστομωτικό κλάδο. Για τον σκοπό αυτό χρησιμοποιούνται συμπεράσματα από τη διεθνή βιβλιογραφία γύρω από τους παράγοντες που μπορεί να οδηγήσουν στην ανάπτυξη στενώσεων, καθώς και κατευθυντήριες γραμμές για την διαμόρφωση των γεωμετρικών μοντέλων Στο πρώτο κομμάτι γίνεται μία αναφορά στις κυριότερες καρδιαγγειακές παθήσεις, που αποτελούν και την υπ αριθμόν ένα αιτία θανάτου παγκοσμίως. Γίνεται αναφορά στους επεμβατικούς τρόπους αντιμετώπισης της στεφανιαίας νόσου με έμφαση στην αορτοστεφανιαία παράκαμψη (bypass). Ακολουθεί μία σύντομη επισκόπηση της βιβλιογραφίας και εξαγωγή των βασικών συμπερασμάτων που θα αποτελέσουν την βάση για την κριτική των αποτελεσμάτων. Εν συνεχεία επεξηγείται αναλυτικά ο τρόπος με τον οποίο παράγονται τα γεωμετρικά μοντέλα, καθώς και οι περιπτώσεις που αναλύθηκαν. Ακολουθεί ο τρόπος κατασκευής του υπολογιστικού πλέγματος, πάνω στο οποίο επιλύονται οι εξισώσεις Navier- Stokes για ασυμπίεστο ρευστό. Τέλος με βάση τα αποτελέσματα από την εκτέλεση του κώδικα για όλες τις περιπτώσεις γίνεται μία προσπάθεια για εξαγωγή συμπερασμάτων. Εξάγονται με βάση την μελέτη των μοντέλων κάποιες ενδεικτικές κατευθυντήριες γραμμές ως προς το ποιες γεωμετρίες και τρόποι αναστόμωσης τείνουν να ευνοήσουν περισσότερο την ανάπτυξη της αθηρωματικής πλάκας αλλά και ποιες αποκαθιστούν την ροή του αίματος. / The subject of the following thesis is the study of the unsteady blood flow in the coronary arteries of the heart in normal conditions, during stenotic conditions and after restoration of the flow with an anastomotic branch. For this purpose, we use the conclusions from the international literature on the factors that can lead to the further development of stenoses, as well as guidelines on the formation of the geometrical models. In the first part we reference the most significant pathologic conditions of the heart which are the number one leading cause of death world widely. We also mention the invasive techniques with which doctors treat the coronary heart disease, emphasizing on the aorto-coronary bypass technique. Furthermore there is a review on the literature on the subject and extraction of the main conclusions we are going to use in the evaluation of the computational results We continue explaining in detail the way that the geometrical models where produced, as well as the cases which were analyzed. There is also an explanation of the way we constructed the computational grids on which we solve the incompressible Navier – Stokes equations. Finally, based on the computational results we obtain by executing the program for all the different cases we extract the basic conclusions. Based on the study of the models we try to give some basic guidelines regarding which geometries and anastomotic techniques tend to favor the further development of the atherosclerotic plaques , but also which ones restore the blood flow to the normal levels

The aim of this study is to create CFD tools and models capable of simulating pulsatile blood flow in abdominal aortic aneurysm (AAA) and stent graft. It helps to increase the current physiological understanding of rupture risk of AAA and stent graft fixation or migration. Firstly, in order to build a general solver for the AAA modeling with reasonable accuracy, a third/fourth order modified OCI scheme is originally developed for general numerical simulation. The modified OCI scheme has a wider cell Reynolds number limitation. This high order scheme performs well with general rectangular mesh for incompressible fluid. Second, a velocity based finite volume method is originally developed to calculate the stress field for solid in order to capture the transient changes of the blood vessel since the artery is a rubber like material. All one, two and three dimensional classical cases for solid are tested and good results are obtained. The velocity based finite volume method show good potential to calculate the stress field for solid and easy to blend with the finite volume fluid solver. It has been recognized that fluid structure interaction (FSI) is very crucial in biomechanics. In this regard, the velocity based finite volume method is then further developed for FSI application. A well known one dimensional piston problem is studied to understand the feasibility of the fluid structure coupling. The numerical prediction matches the analytical solution very well. The velocity based method introduces less numerical damping compared with a stagger method and a monolithic method. Finally, the work focuses on practical pulsatile boundary conditions, non-Newtonian blood viscous properties and bifurcating geometry, and provides an overview of the hemodynamic within the AAA model. A modified Womersley inlet and imbalance pressure outlet boundary conditions are originally used in this study. The Womersley inlet boundary represents better approximation for pulsatile flow compared with the parabolic inlet condition. Numerical results are presented providing comparison between different boundary conditions using different viscous models in both 2D and 3D aneurysms. Good agreement between the numerical predictions and the experimental data is achieved for 2D case. 3D stent models with different bifurcation angles are also tested. The Womersley inlet boundary condition improves the existing inlet conditions significantly and it can reduce the Aneurysm neck computation domain. The influence of the non-Newtonian model to the wall shear stress (WSS) and strain-rate is also studied. The non-Newtonian model tends to produce higher WSS at both proximal and distal end of the aneurysm as compared with the Newtonian model (both 2D and 3D cases). The computed strain-rate distribution at the centre of the aneurysm is different between these two models. The influence of imbalance outlet pressure at the iliac arteries to the blood flow is originally investigated. The imbalance outlet pressure boundary conditions affect the computed wall shear stress significantly near the bifurcation point. All the pulsatile Womersley inlet, non-Newtonian viscosity properties and the imbalance pressure outlet need to be considered in blood flow simulation of AAA.

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